Timing of clinical improvement and symptom resolution in the treatment of major depressive disorder (original) (raw)
Related papers
Onset, time course and trajectories of improvement with antidepressants
European Neuropsychopharmacology, 2012
There is still considerable controversy about the onset and time course of improvement with antidepressants in the treatment of major depressive disorder. Previous studies suggested a delayed-onset hypothesis with therapeutic improvement taking several weeks, but recent metaanalyses have shown support for earlier onset of improvement within the first week or two of treatment. This paper briefly reviews the evidence, focused on antidepressant studies published since 2006, for early onset of improvement within the first 2 weeks of treatment. A PubMed electronic search was conducted with selection of relevant studies from 2007 to March 2012. With the caveat of methodological limitations, results from randomized clinical trials, meta-analyses and naturalistic studies consistently show that: (1) antidepressants in general have early onset of improvement, (2) some antidepressants, including the novel mechanism agent, agomelatine, are associated with early improvement in both core and specific symptoms such as anhedonia and sleep-wake disturbances, and (3) early improvement predicts sustained response and remission. Use of newer statistical methods to examine individual response trajectories may address some of the methodological limitations of previous studies. The predictive value of early improvement has important clinical relevance for antidepressant treatment. Measurement-based assessment for response should occur earlier and more frequently. A lack of improvement (defined as r20% reduction from baseline in scores on a depression rating scale) at 2-3 weeks after initiation of an antidepressant should prompt the clinician to consider a change in management.
Psychopharmacology, 2014
Rationale Traditionally, the therapeutic effect of antidepressants is thought to take several weeks. However, several studies found evidence of early drug response occurring within the first 2 weeks of antidepressant treatment and that this early onset response may predict eventual treatment outcome. Objective This study aims to investigate the predictive value of early improvement in the course of treatment with imipramine or venlafaxine in an inpatient population with severe major depression. Method A post hoc analysis was conducted after pooling data from two almost identical trials. The study included 149 patients with DSM-IV diagnosis major depression and a baseline score ≥17 on the 17-item Hamilton Rating Scale for Depression (HAM-D). Patients were randomized for doubleblind treatment with either antidepressant. Early improvement (≥25 % reduction on HAM-D score) was evaluated after 2 weeks and response (≥50 % reduction on HAM-D score) after 6 weeks of acute treatment. Results Of 64 patients achieving early improvement, 38 (59 %) became responders, whereas of 85 patients not achieving early improvement, only 23 (27 %) became responders. There was a significant difference in time to response between patients achieving early improvement and patients not achieving early improvement. Early improvement is a modest sensitive predictor for eventual response. Conclusion In the present study, although the sensitivity of early improvement was modest, based on the severity of clinical symptoms, a clinician treating a patient with severe major depression may seriously consider changing the treatment at an earlier stage than is presently customary.
2009
Background: It is uncertain as to what short-term outcomes predict long-term treatment compliance and outcomes in patients with MDD. Aims: To determine what treatment milestones predict symptom remission with long-term treatment with antidepressant medication. Method: Pooled analysis of four randomised, double-blind, active comparator, 6-month trials in MDD. Results: Patients received double-blind treatment with escitalopram (N = 699) or a comparator (citalopram, duloxetine, or paroxetine) (N = 699). Onset of effect at week 2 was correlated with response at week 8, and response at week 8 with completion of 6-month treatment. Week 8 response was associated with a greater probability of achieving later remission. Week 24 remission (MADRS P 10) was significantly (p < 0.01) higher for patients treated with escitalopram (70.7%) than for the pooled comparators (64.7%). Week 24 complete remission (MADRS 6 5) was significantly (p < 0.01) higher for escitalopram (51.7%) than for the pooled comparators (45.6%). Fewer patients discontinued treatment with escitalopram (15.9%) than with the pooled comparators (23.9%) (p < 0.001). Conclusion: A higher probability of achieving remission is associated with responding after 8 weeks and with completing 6 months of treatment.
Journal of Affective Disorders, 2010
Background: There is substantial evidence that early improvement (EI) under antidepressant treatment is a clinically useful predictor of later treatment outcome in patients with major depressive disorders. The aim of this study was to test whether EI can also be used as a predictor for treatment outcome in patients with mild major, minor or subsyndromal depression, i.e. patients, who are typically treated by general practitioners. Methods: Analyses were carried out using data from 223 patients of a 10-weeks randomized, placebo-controlled trial comparing the effectiveness of sertraline and cognitive-behavioural therapy (CBT) in patients with mild major, minor or subsyndromal depression. EI was defined as a reduction of ≥ 20% on the 17-item Hamilton Rating Scale for Depression (HAMD-17) compared with baseline within the first 2 weeks of treatment. The predictive value of EI for stable response at week 8 and 10 (≥ 50% HAMD-17 sum score reduction at weeks 8 and 10) and stable remission (HAMD-17 sum score ≤ 7 at weeks 8 and 10) was evaluated. Results: In both the sertraline-and CBT-treatment group, EI was a highly sensitive predictor for later stable response (76% and 82%, respectively) and stable remission (70% and 75%, respectively). In patients without EI, only a small proportion of sertraline or CBT-treated patients achieved stable response (20.9% and 5.9%, respectively) or stable remission (18.6% and 8.8%, respectively). Patients with EI were by far more likely to achieve stable response or stable remission than patients without as indicated by high odds ratios (95% confidence interval) of 8.1 (3.0-21.8) and 3.8 (1.4-10.1) for sertraline, and 11.1 (2.1-58.4) and 7.2 (1.7-30.8) for CBT-treated patients, respectively. Limitations: Sample sizes were relatively low in different treatment groups. Conclusion: The identification of early improvement might be useful in clinical decision making in the early course of treatment of patients with mild major, minor and subthreshold depression.
Journal of Clinical Psychopharmacology, 2016
Our objective was to validate the different versions of the Hamilton Depression Scale (HAM-D) both psychometrically (scalability) and clinically in discriminating antidepressants from placebo in terms of remission rates in an 8-week clinical trial in the acute treatment of major depression. The traditional HAM-D 17 version was compared with the shorter HAM-D 6 and the longer HAM-D 21 or HAM-D 24 in a fixed-dose placebocontrolled vortioxetine study. Clinical Global Impression of Severity scores were used to establish standardized cutoff scores for remission across each scale. Using these cutoff scores, we compared the ability of each scale to separate drug-placebo remission rates, evaluated by the number needed to treat for clinical evidence. The HAM-D 6 was superior to HAM-D 17 in separating drug-placebo remission rates at the end point, defined as number needed to treat of less than 10. More items in the longer HAM-D versions indicated smaller discriminating validity over placebo. The HAM-D 6 indicated a dose effect on remission for vortioxetine in both moderate and severe major depression. The brief HAM-D 6 was thus found superior to HAM-D 17 , HAM-D 21 , and HAM-D 24 both in terms of scalability and in discriminating antidepressants from placebo.
Objective: To describe a brief depression rating scale capable of estimating depression symptom severity, establishing and comparing the efficacy of antidepressant treatment, and distinguishing a clinical response to treatment from full symptomatic remission. Method: An extraction technique was employed attempting to identify the most commonly endorsed and sensitive depressive items from a standardized clinician-rated depression scale, the 17-Item Hamilton Rating Scale for Depression (HAM-D17). Data was harvested from a mood disorders clinical database within a tertiary university-affiliated hospital. Participants were comprised of patients (N=248) with a diagnosis of major depressive disorder who were receiving naturalistic treatment. The primary aim of this study was to identify a cutoff score to distinguish clinical response from remission. Results: A score of ≤3 (out of a potential score of 26) would define a full remission of symptoms with the Toronto Hamilton Depression Rating Scale. Conclusion: Family physicians prescribing antidepressant treatment should employ a brief valid comprehensive scale to assess depression severity at baseline and monitor patient response to treatment. The contemporary goal in treating depressed patients is full remission of symptoms. Full remission has been operationalized quantitatively inviting the need for depression rating scales in the routine management of all depressed patients.
Human Psychopharmacology: Clinical and Experimental, 1995
In a double‐blind multicentre trial in patients with major depression, the efficacy and the tolerability of sertraline were compared with those of fluoxetine, during an eight‐week acute treatment phase followed by a 24‐week continuation treatment phase in treatment responders.A total of 165 patients who met DSM III‐R criteria for moderate to severe major depression were randomized to receive either sertraline or fluoxetine for short‐term and continuation treatment with initial daily dosages of either 50 mg of sertraline or 20 mg of fluoxetine. In the event of an inadequate response after 4 weeks of double‐blind therapy these doses could be doubled.Both treatment groups demonstrated similar improvements on both the Hamilton Rating Scale for Depression (HAM‐D) and the Montgomery and Asberg Depression Rating Scale (MADRS), during the acute phase as well as during the continuation phase. Both sertraline and fluoxetine were well tolerated, the most common side‐effects being gastrointesti...
Timing of Onset of Antidepressant Response With Fluoxetine Treatment
American Journal of Psychiatry, 2000
The purpose of this study was to assess the time until onset of antidepressant response with fluoxetine treatment. Method: The authors evaluated 182 outpatients with major depression who had a sustained acute response to fluoxetine treatment. The outpatients received 8 weeks of treatment with 20 mg/day of fluoxetine and were assessed biweekly with the 17-item Hamilton Depression Rating Scale. The onset of response was defined as a 30% decrease in score on the Hamilton depression scale that persisted and led to a 50% decrease by week 8. The Kaplan-Meier product limit and Cox regression analysis were used to model the relationship between relevant variables and time until onset of response. Results: The authors found that at weeks 2, 4, and 6, the probabilities of having an onset of response (for responders) were 55.5%, 24.7%, and 9.3%, respectively. The cumulative probabilities of onset of response at each time point were 55.5%, 80.2%, and 89.5%. Neither demographics nor clinical characteristics of depression predicted time until initial response. Conclusions: These data suggest that more than half of eventual responders to fluoxetine treatment at 8 weeks start to respond by week 2; over 75% start to respond by week 4. Conversely, the lack of onset of response at 4-6 weeks was associated with about a 73%-88% chance that patients would not have an onset of response by 8 weeks.